Scale-up and standardization of the solid-phase synthesis of a peptide for the treatment of patients with Rheumatoid Arthritis and COVID-19
Abstract
The CIGB-814 peptide was initially designed to treat patients with Rheumatoid Arthritis (RA); however, the expansion of its use to COVID-19 patients during
the pandemic led to a required increment of the peptide manufacturing capacity. There was no standardized large-scale solid-phase synthesis (SPPS)
procedure to produce it in compliance with Good Manufacturing Practices (GMP). The primary objective of the study was to standardize an SPPS
procedure to produce the CIGB-814 peptide using up to 200 g of MBHA resin. First, the SPPS procedure was scaled up and established for 50 g of MBHA
resin by applying the rule of thumb, evaluating two scale-up criteria (power per unit volume (P/V) and nozzle tip velocity (DTI)). The experimental conditions
were standardized to 200 g of MBHA resin, combined with the determination of peptide identity by mass spectrometry and purity by RP-HPLC. The reaction conditions were studied, obtaining that at 200 g of MBHA resin and a stirring speed of 80 min-1, 25 °C, in a 20/20 cm/cm height/diameter geometry reactor, the mass of the crude CIGB-814 peptide increases up to fourfold, the yield at 7.5%, maintaining the purity of the material; with the same total consumption of organic solvents in the same time interval. In conclusion, the scaling and standardization of the SPFS for the production of the CIGB-814 peptide under GMP at a scale of 200 g of MBHA resin meets the demand for the biopharmaceutical product Jusvinza® designed to treat patients with RA and COVID-19.
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